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LightThinker++: From Reasoning Compression to Memory Management

arXiv:2604.03679v1 Announce Type: cross Abstract: Large language models (LLMs) excel at complex reasoning, yet their efficiency is limited by the surging cognitive overhead of long thought traces. In this paper, we propose LightThinker, a method that enables LLMs to dynamically compress intermediate thoughts into compact semantic representations. However, static compression often struggles with complex reasoning where the irreversible loss of intermediate details can lead to logical bottlenecks. To address this, we evolve the framework into LightThinker++, introducing Explicit Adaptive Memory Management. This paradigm shifts to behavioral-level management by incorporating explicit memory primitives, supported by a specialized trajectory synthesis pipeline to train purposeful memory scheduling. Extensive experiments demonstrate the framework's versatility across three dimensions. (1) LightThinker reduces peak token usage by 70% and inference time by 26% with minimal accuracy loss. (2) In standard reasoning, LightThinker++ slashes peak token usage by 69.9% while yielding a +2.42% accuracy gain under the same context budget for maximum performance. (3) Most notably, in long-horizon agentic tasks, it maintains a stable footprint beyond 80 rounds (a 60%-70% reduction), achieving an average performance gain of 14.8% across different complex scenarios. Overall, our work provides a scalable direction for sustaining deep LLM reasoning over extended horizons with minimal overhead.
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Integrated proteomics and metabolomics analysis reveals mechanisms by which SFYC decoction regulates airway inflammation in asthma

J Ethnopharmacol. 2026 Mar 30;365:121612. doi: 10.1016/j.jep.2026.121612. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Airway inflammation is one of the primary pathological characteristics of asthma. Soufeng Yuchuan (SFYC) decoction, a compound formula derived from multiple traditional Chinese medicine prescriptions, is widely applied clinically and exhibits significant therapeutic efficacy against asthma. However, its anti-asthmatic mechanisms remain incompletely understood.

MATERIALS AND METHODS: Asthmatic rat models induced by ovalbumin (OVA) and ferroptosis models induced by erastin in BEAS-2B cells were established. Proteomics and metabolomics analyses were conducted on lung tissues and serum. Key ferroptosis-related targets (GPX4, SLC7A11/SLC3A2, GCLC, GSS, and VDAC2) were validated using Western blotting, RT-qPCR, and biochemical assays. The direct anti-ferroptosis effects of SFYC-containing serum were compared with ferrostatin-1 and blank serum in vitro.

RESULTS: Integrated omics analysis revealed that ferroptosis, glutathione metabolism, and ROS signaling pathways were the core targets modulated by SFYC. In vivo, SFYC significantly reduced airway inflammation and ROS accumulation, restored pulmonary GSH levels, upregulated the expression of GPX4, GCLC, GSS, SLC7A11, and SLC3A2, and downregulated VDAC2 expression (P < 0.05). In vitro, SFYC-containing serum effectively reversed erastin-induced lipid peroxidation, iron overload, GSH depletion, ROS elevation, and apoptosis in BEAS-2B cells, demonstrating comparable or superior efficacy to ferrostatin-1.

CONCLUSION: SFYC alleviates airway inflammation in asthma primarily by inhibiting ferroptosis. This study provides evidence that SFYC exerts anti-asthmatic effects, at least in part, via the regulation of ferroptosis pathways.

PMID:41921764 | DOI:10.1016/j.jep.2026.121612

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New perspectives in immunotherapy for hepatocellular carcinoma: Focusing on resistance mechanism, biomarker, and personalized treatment

Crit Rev Oncol Hematol. 2026 Mar 27;222:105305. doi: 10.1016/j.critrevonc.2026.105305. Online ahead of print.

ABSTRACT

The management of hepatocellular carcinoma (HCC) faces substantial and evolving challenges, driven by its aggressive biology, drug resistance, and the clinical urgency to detect recurrence. The treatment paradigm has undergone a profound transformation, evolving from surgical interventions and molecular targeted agents to the current era dominated by immunotherapy. Immune checkpoint inhibitors, particularly when used in combination with anti-angiogenic drugs or as part of dual-checkpoint blockade regimens, have established a new first-line standard of treatment for advanced HCC, delivering unprecedented survival improvements. Despite this progress, significant obstacles remain, including primary and acquired resistance, variable patient responses, and notably reduced efficacy in specific etiological subgroups. This comprehensive review synthesizes the emerging modalities such as bispecific antibodies, adoptive cell therapies, and innovative rational combinations that integrate systemic immunotherapy with locoregional treatments or novel targeted agents. Furthermore, we delve into the critical search for predictive biomarkers, encompassing liquid biopsy and multi-omics approaches, and dissect the complex cellular and molecular mechanisms underlying therapeutic resistance within the immunosuppressive tumor microenvironment. Finally, we outline future translational directions, emphasizing the expansion of immunotherapy, the development of tailored strategies for therapy-resistant disease, and the imperative move towards a personalized, biomarker-driven treatment framework. This review provides a cohesive overview of the field and charts a roadmap for future research to overcome the current challenges in HCC immunotherapy.

PMID:41905572 | DOI:10.1016/j.critrevonc.2026.105305

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tRF-3005a regulates exon skipping of SPAG4 by interacting with RALY to drive gastric cancer progression

Cell Death Discovery, Published online: 24 March 2026; doi:10.1038/s41420-026-03049-3

tRF-3005a regulates exon skipping of SPAG4 by interacting with RALY to drive gastric cancer progression
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From Black Box to Biological Insight: AttentioFuse Unlocks Multi-Omics Dynamics in Lung Cancer

Cancers (Basel). 2026 Mar 9;18(5):878. doi: 10.3390/cancers18050878.

ABSTRACT

BACKGROUND: Lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), the major subtypes of non-small cell lung cancer (NSCLC), exhibit distinct molecular landscapes that demand precision in prognosis and therapy. While deep learning models can achieve high predictive accuracy, their black-box nature limits clinical translation.

METHODS: We introduce AttentioFuse, an interpretable deep learning framework employing a Reactome-guided mid-fusion strategy for multi-omics integration. AttentioFuse builds on three pillars: (i) dual-phase learning with omics-specific encoders to preserve modality-unique patterns, (ii) hierarchical attention mechanisms (cross-omics, feature-level, and fusion-layer) to quantify layer contributions dynamically, and (iii) integrated explainability combining DeepSHAP and global attention weights for gene-to-pathway interpretation. Two depth variants are instantiated under identical priors: a three-layer configuration (3F) for main discrimination and a five-layer configuration (AttentioFuse-5X) for deeper hierarchical interpretation; the 5X variant is trained end-to-end and yields comparable accuracy while enhancing pathway-level resolution.

RESULTS: Evaluated on The Cancer Genome Atlas (TCGA) LUAD/LUSC cohorts, AttentioFuse matches state-of-the-art performance in TNM staging while uncovering actionable biological insights, including pan-NSCLC AKT/mTOR metabolic control, histology-divergent Notch signaling roles, and additional pathways related to developmental reactivation, microbiota-associated metastasis, and extracellular matrix remodeling.

CONCLUSIONS: By design, AttentioFuse-5X bridges predictive performance with hierarchical, pathway-resolved explanations, advancing oncology by transforming black-box predictions into biologically grounded decision support.

PMID:41827812 | PMC:PMC12985206 | DOI:10.3390/cancers18050878

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From Black Box to Biological Insight: AttentioFuse Unlocks Multi-Omics Dynamics in Lung Cancer

Cancers (Basel). 2026 Mar 9;18(5):878. doi: 10.3390/cancers18050878.

ABSTRACT

BACKGROUND: Lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), the major subtypes of non-small cell lung cancer (NSCLC), exhibit distinct molecular landscapes that demand precision in prognosis and therapy. While deep learning models can achieve high predictive accuracy, their black-box nature limits clinical translation.

METHODS: We introduce AttentioFuse, an interpretable deep learning framework employing a Reactome-guided mid-fusion strategy for multi-omics integration. AttentioFuse builds on three pillars: (i) dual-phase learning with omics-specific encoders to preserve modality-unique patterns, (ii) hierarchical attention mechanisms (cross-omics, feature-level, and fusion-layer) to quantify layer contributions dynamically, and (iii) integrated explainability combining DeepSHAP and global attention weights for gene-to-pathway interpretation. Two depth variants are instantiated under identical priors: a three-layer configuration (3F) for main discrimination and a five-layer configuration (AttentioFuse-5X) for deeper hierarchical interpretation; the 5X variant is trained end-to-end and yields comparable accuracy while enhancing pathway-level resolution.

RESULTS: Evaluated on The Cancer Genome Atlas (TCGA) LUAD/LUSC cohorts, AttentioFuse matches state-of-the-art performance in TNM staging while uncovering actionable biological insights, including pan-NSCLC AKT/mTOR metabolic control, histology-divergent Notch signaling roles, and additional pathways related to developmental reactivation, microbiota-associated metastasis, and extracellular matrix remodeling.

CONCLUSIONS: By design, AttentioFuse-5X bridges predictive performance with hierarchical, pathway-resolved explanations, advancing oncology by transforming black-box predictions into biologically grounded decision support.

PMID:41827812 | PMC:PMC12985206 | DOI:10.3390/cancers18050878

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